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Astroglial Connexin43 as a Potential Target for a Mood Stabiliser

Department of Neuropsychiatry, Division of Neuroscience, Graduate School of Medicine, Mie University, Tsu 514-8507, Japan
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(1), 339;
Received: 18 November 2020 / Revised: 24 December 2020 / Accepted: 27 December 2020 / Published: 30 December 2020
(This article belongs to the Special Issue Molecular Mechanisms of Mood Stabilizers)
Mood disorders remain a major public health concern worldwide. Monoaminergic hypotheses of pathophysiology of bipolar and major depressive disorders have led to the development of monoamine transporter-inhibiting antidepressants for the treatment of major depression and have contributed to the expanded indications of atypical antipsychotics for the treatment of bipolar disorders. In spite of psychopharmacological progress, current pharmacotherapy according to the monoaminergic hypothesis alone is insufficient to improve or prevent mood disorders. Recent approval of esketamine for treatment of treatment-resistant depression has attracted attention in psychopharmacology as a glutamatergic hypothesis of the pathophysiology of mood disorders. On the other hand, in the last decade, accumulated findings regarding the pathomechanisms of mood disorders emphasised that functional abnormalities of tripartite synaptic transmission play important roles in the pathophysiology of mood disorders. At first glance, the enhancement of astroglial connexin seems to contribute to antidepressant and mood-stabilising effects, but in reality, antidepressive and mood-stabilising actions are mediated by more complicated interactions associated with the astroglial gap junction and hemichannel. Indeed, several depressive mood-inducing stress stimulations suppress connexin43 expression and astroglial gap junction function, but enhance astroglial hemichannel activity. On the other hand, monoamine transporter-inhibiting antidepressants suppress astroglial hemichannel activity and enhance astroglial gap junction function, whereas several non-antidepressant mood stabilisers activate astroglial hemichannel activity. Based on preclinical findings, in this review, we summarise the effects of antidepressants, mood-stabilising antipsychotics, and anticonvulsants on astroglial connexin, and then, to establish a novel strategy for treatment of mood disorders, we reveal the current progress in psychopharmacology, changing the question from “what has been revealed?” to “what should be clarified?”. View Full-Text
Keywords: depression; bipolar disorder; mood stabiliser; astrocytes; connexin; tripartite synaptic transmission depression; bipolar disorder; mood stabiliser; astrocytes; connexin; tripartite synaptic transmission
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MDPI and ACS Style

Okada, M.; Oka, T.; Nakamoto, M.; Fukuyama, K.; Shiroyama, T. Astroglial Connexin43 as a Potential Target for a Mood Stabiliser. Int. J. Mol. Sci. 2021, 22, 339.

AMA Style

Okada M, Oka T, Nakamoto M, Fukuyama K, Shiroyama T. Astroglial Connexin43 as a Potential Target for a Mood Stabiliser. International Journal of Molecular Sciences. 2021; 22(1):339.

Chicago/Turabian Style

Okada, Motohiro, Tomoka Oka, Misaki Nakamoto, Kouji Fukuyama, and Takashi Shiroyama. 2021. "Astroglial Connexin43 as a Potential Target for a Mood Stabiliser" International Journal of Molecular Sciences 22, no. 1: 339.

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